Critical and diverse role of alarmin cytokines in parasitic infections
Review
. 2024 Nov 4:14:1418500.
doi: 10.3389/fcimb.2024.1418500.
eCollection 2024.
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Review
Front Cell Infect Microbiol.
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Abstract
Alarmin cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) function as danger signals to trigger host immunity in response to tissue injury caused by pathogenic factors such as parasitic infections. Parasitic diseases also provide an excellent context to study their functions and mechanisms. Numerous studies have indicated that alarmin cytokine released by non-immune cells such as epithelial and stromal cells induce the hosts to initiate a type 2 immunity that drives parasite expulsion but also host pathology such as tissue injury and fibrosis. By contrast, alarmin cytokines especially IL-33 derived from immune cells such as dendritic cells may elicit an immuno-suppressive milieu that promotes host tolerance to parasites. Additionally, the role of alarmin cytokines in parasite infections is reported to depend on species of parasites, cellular source of alarmin cytokines, and immune microenvironment, all of which is relevant to the parasitic sites or organs. This narrative review aims to provide information on the crucial and diverse role of alarmin cytokines in parasitic infections involved in different organs including intestine, lung, liver and brain.
Keywords:
IL-25; IL-33; TSLP; parasitic infection; type 2 immunity.
Copyright © 2024 Xing, Liu and He.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures
Figure 1
The roles and mechanisms of alarmin cytokines in intestinal parasitic infections. IL-25 and IL-33 can elicit both protective immunity and immune tolerance in intestine during infections. (A) Protective immunity. Parasites can cause the damage of intestinal epithelial cells (IECs) which results in the release of IL-33 from these cells. The injured IECs also release ATP which induce the mast cells to secret IL-33 through binding to P2X7R. Moreover, the intact IECs can actively secret IL-33 via GSDMC membrane pores after the activation of IL4Rα signaling. Epithelial tuft cells are the sole source of IL-25 in the gut. The metabolites such as succinate from intestinal parasites especially some protist can trigger the tuft cells to secret IL-25 through interaction with taste receptors such as SUCNR1. Both IL-25 and IL-33 can activate group 2 innate lymphoid cells (ILC2s) which express IL-25 receptor IL17R and IL-33 receptor ST2. IL-13 released from activated ILC2s promotes the activation of Th2 cells which produce Th2 cytokines such as IL-4 and IL-13. Th2 cytokines from both ILC2s and Th2 cells instruct the gut mucosa to mount a “weep and sweep” response to expel gut parasites through IL4Rα signaling. Th2 cytokines can also amplify the response of IECs and tuft cell to parasite invasion through IL4Rα signaling. Thus, the positive feed forward loop comprised of IECs, tuft cells, ILC2s, and Th2 cells is the main host defense mechanism against intestinal parasites. (B) Immune tolerance. Myeloid cells such as DCs release IL-33 through the inducible transmembrane pore-forming protein perforin-2. DC-derived IL-33 activates the ST2 positive intestinal Tregs which suppress the activation of Th2 cells. IL-25 induces B1 cell IgE production which blocks the activation of mast cells. H. polygyrus has evolved several mechanisms to negate the function of IL-33. Soluble excretory protein H. polygyrus alarmin release inhibitor (HpARI) can blocks the function of IL-33 by binding the intracellular and extracellular IL-33. Another soluble excretory protein H. polygyrus binds alarmin receptor and inhibits (HpBARI) can bind membrane ST2 which prevents IL-33-ST2 interactions.
Figure 2
The diverse role of alarmin cytokines in parasitic infections. The invasion of parasites leads to the release of alarmin cytokines from the damaged or stimulated epithelial cells. These cytokines activate ILC2 to mount a protective immunity but also cause host tissue injury or fibrosis. By contrast, the invasion of parasites may simultaneously stimulate the immune cells such as DC to release IL-33. The IL-33 derived from DC activates Treg to mount a tolerance immunity but also prevent host pathology.
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MeSH terms
Grants and funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (No. 81871678, 82173640, and 82322061).
Fonte original PubMed